Francois Vigneault (Shape Therapeutics)

EX­CLU­SIVE: Shape Ther­a­peu­tics rais­es $112M in bid to make RNA edit­ing — and a whole lot else — a re­al­i­ty

Two years af­ter spin­ning out of CRISPR pi­o­neer Prashant Mali’s lab, Shape Ther­a­peu­tics has a lot more cash and a slight­ly new mis­sion.

The com­pa­ny orig­i­nal­ly launched in 2019 with plans to de­vel­op ther­a­pies around a new form of gene edit­ing, one they hoped could bet­ter ad­dress cer­tain dis­eases than CRISPR or oth­er forms of gene ma­nip­u­la­tions. That’s still their goal, but CEO Fran­cois Vi­gneault has added a few oth­ers in the mean­time.

“The com­pa­ny re­al­ly start­ed as, how can we find a so­lu­tion to some of the lim­i­ta­tions of gene edit­ing?” Vi­gneault said. “But from there, we quick­ly re­al­ized there was a mas­sive bot­tle­neck in an­oth­er sphere of gene ther­a­py.”

Shape end­ed up spend­ing con­sid­er­able time and re­sources try­ing to de­vel­op and make broad­ly avail­able so­lu­tions to two of the biggest con­straints that have held up the broad­er field: man­u­fac­tur­ing and de­liv­ery. They’ll now have a lot more mon­ey to do so and bring for­ward their own med­i­cines, an­nounc­ing a $112 mil­lion Se­ries B on Thurs­day led by Decheng Cap­i­tal and Bre­ton Cap­i­tal.

Shape spe­cial­izes in RNA edit­ing; the com­pa­ny tries to de­vel­op ther­a­pies that in­ter­cept the bro­ken mes­sages that the DNA of pa­tients with cer­tain dis­eases sends out and cor­rect it be­fore it gets turned in­to pro­teins. That con­trasts with CRISPR and oth­er gene edit­ing ap­proach­es that try to di­rect­ly — and per­ma­nent­ly – al­ter DNA.

It does so by ex­ploit­ing a nat­u­ral­ly oc­cur­ring en­zyme that’s al­ready present in hu­man cells called ADAR. By send­ing in their own spe­cial­ly con­struct­ed strand of guide RNA, re­searchers can in the­o­ry re­cruit this en­zyme and get it to ma­nip­u­late spe­cif­ic strands of mes­sen­ger RNA in par­tic­u­lar ways. They could, for ex­am­ple, delete or add bases.

Shape is fo­cus­ing their ef­forts on neu­rons, where ADAR seems to work par­tic­u­lar­ly well — pos­si­bly be­cause it’s nat­u­ral­ly high­ly ex­pressed — and where, by con­trast, CRISPR com­pa­nies have had par­tic­u­lar dif­fi­cul­ty ap­ply­ing their more well-known tech­nol­o­gy. They have lead pro­grams in the rare ge­net­ic dis­ease Rett syn­drome and Parkin­son’s.

In de­vel­op­ing those ther­a­pies, Vi­gneault and his col­leagues ran square in­to the prob­lems every gene ther­a­py com­pa­ny has hit dur­ing the field’s 2010s resur­gence. The vi­ral vec­tors used to shut­tle genes (or in this case, RNA) are dif­fi­cult to man­u­fac­ture at scale. And it’s dif­fi­cult to de­vel­op ones that go pre­cise­ly to the right tis­sue and the right kind of cell in hu­mans.

“We found this [tech­nol­o­gy] is a ma­jor ad­van­tage in neu­rons and CNS dis­or­ders,” Vi­gneault said. “But on the de­liv­ery front what we dis­cov­er is a huge lim­i­ta­tion.”

So Shape en­gi­neered a cell line they claim can pro­duce more ade­no-as­so­ci­at­ed virus (AAV), the most com­mon vi­ral vec­tor used in gene ther­a­py, than any oth­er method. And they in­vest­ed in the tech­nol­o­gy to en­gi­neer AAVs, screen­ing mil­lions of AAVs in cells and mon­keys to de­vel­op ones par­tic­u­lar­ly suit­ed to reach­ing neu­rons or mus­cles.

That puts Shape in di­rect com­pe­ti­tion with com­pa­nies such as Affinia and Dyno, which are ded­i­cat­ed sole­ly to AAV en­gi­neer­ing and have raised hun­dreds of mil­lions of dol­lars and signed bil­lion-dol­lar deals with Big Phar­ma for their vec­tors.

Vi­gneault said Shape will sim­i­lar­ly try to make their AAV and cell lines avail­able to oth­er groups in in­dus­try and acad­e­mia, while con­tin­u­ing to de­vel­op their own ther­a­pies in house and with larg­er com­pa­nies. They have broad am­bi­tions there, too, re­cent­ly up­dat­ing their “pipeline” on­line to show, rather than the few pro­grams clos­est to the clin­ic, a con­stel­la­tion of the dozens of dis­eases they be­lieve their ADAR tech is best suit­ed for, from Alzheimer’s to cys­tic fi­bro­sis.

“The idea is to build a slight­ly dif­fer­ent com­pa­ny than the typ­i­cal one,” Vi­gneault said. “First make a tool that’s dis­rup­tive, not an in­cre­men­tal im­prove­ment, and when you have that tool, make it avail­able so that you can help as many pa­tients as pos­si­ble be­cause one com­pa­ny can’t do it all.”

Cor­rec­tion: The ar­ti­cle has been to clar­i­fy Shape spun out of the Mali lab, not the Church lab.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, Congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Bio­gen, Ei­sai are push­ing for an­oth­er ac­cel­er­at­ed Alzheimer's OK — this time for BAN2401

Now that the door at the FDA has been opened wide for Alzheimer’s drugs that can demonstrate a reduction in amyloid, Biogen and its partners at Eisai are pushing for a quick OK on the next drug to follow in the controversial path of aducanumab.

In a presentation to analysts, Eisai neurology chief Ivan Cheung outlined some bullish expectations for their newly-approved treatment and set the stage for what he believes will be a fast follow for BAN2401 (lecanemab) — after a dry spell in new drug development that’s lasted close to 20 years.

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Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

UP­DAT­ED: Sanofi buys mR­NA play­er Trans­late Bio for $3.2B. And the price fits a pop­u­lar range for biotech M&A

Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio $TBIO a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines, Sanofi closed the deal with a buyout early Tuesday, spending $38 a share in a $3.2 billion buyout.

Translate’s stock $TBIO soared after the market closed Monday when Reuters reported the first word of the acquisition just hours ahead of the formal announcement. The wire service, though, didn’t have a price to report in its scoop, and investors chased the stock up 78% in the wild ride that followed. Once the price was announced, gains shriveled to 29% ahead of the bell.

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